1. Field of the Invention
The present invention is directed to a method for the topical application of opioid analgesic drugs such as morphine. Specifically, the present invention relates to topical application of the opioid drug and specifically a morphine sulphate in a diluted solution to produce a therapeutic effect in an area of itching and/or skin irritations and without a transdermal migration of the opioid drug into the bloodstream.
2. Description of the Prior Art
Itching is an irritating sensation that has some parallels to pain yet is quite different. The mechanisms of pruritus have been closely studied but still are not fully understood. The most likely initiators of the sensation of itching are chemical substances, including endogenous substances like histamine, prostaglandin, epidermal protease, substance P and endopeptides. Lately, some studies have shown that morphine receptors are involved in the mechanism of itching and are studying the use of narcotic antagonists for treatment of itching.
The sensation of itching is conducted slowly along C nerve fibers. Initiation of itching is understood to be the result of certain mediators acting on free nerves ending on the skin within the epidermal junction. Scratching is a unique response to the sensation of itching, thought to be a reflex to remove noxious agents from the skin surface. Scratching brings about a transient sense of relief and may even give pleasure (due to morphine receptors).
Itching may be a localized or generalized phenomenon. Localized itching includes skin disease like psoriasis or scabies or flea bites, which can all produce pruritus. Generalized pruritus can be the result of certain environmental factors, including an excessively dry or humid climate, dry centralized heating, perspiration, overbathing, and harsh soap. The generalized pruritus can also be caused by primary skin disease. Generalized pruritus can also be the result of diseases like internal diseases affecting the endocrine and metabolic-hepatic-renal-hematological system as well as other processes such as cancer. Other causes of itching include injection of drugs like penicillin, drugs which can be harmful to the liver, and illicit drugs.
Treatment:
The optimal therapy for generalized pruritus is treatment of the underlying disease. However, if the etiology has not been determined or if there is no specific treatment, a number of nonspecific palliative therapies exist. Treatment may be topical or systemic. The cooling effect of menthol and the anesthetic effect of phenol or camphor may offer temporary relief for some patients. Low potency topical steroids are good for short term therapy but they are not recommended for chronic use.
When generalized pruritus is treated systemically, it is usually because topical measures have provided no relief. Oral antihistamines are the most commonly used. They act by competitively blocking peripheral histamine receptors, thereby blocking a mode of conduction of itch impulse. The problem with antihistamines is that they produce a sedative effect and rather than directly controlling the itching they could be working by dulling the perception of itching. The problem also is that antihistamines cannot be effective in all cases.
In addition, there have been multiple topical solutions to treat pruritus, including topical capsaicin (Zostrix), which may remove pruritus from patients on hemodialysis. If the pruritus is associated with liver disease, there has been treatment with agents such as rifampin, which are mostly used for tuberculosis, and they have extreme side effects like depression of bone marrow. Of course, there are many other cases where there is no true treatment of pruritus, such as for patients who have diseases that have nonspecific therapies. For example, pruritus or itching associated with AIDS. In those cases many kinds of treatments have been tried without any success, like ultraviolet lights, capsaicin and antihistamines, all without any major relief. Also, the ultraviolet therapy in AIDS patients is bad because ultraviolet affects the T4 lymphocytes and subsequently immunity.
Regardless of its etiology, pruritus which has been present for a long period of time can cause significant frustration for both patients and physician. Thus, it is important for the physician to regularly assess the patient for possible underlying disease and try to find different therapies which will be helpful to the patient without causing any major side effects.
Topical methods:
Combating the urge of scratching is an important part of therapy, so application of a cool, moist washcloth to the area or application of pressure with the palm of the hand near the pruritus area can abate the urge of scratching. Topical preparations may also be used for moisturizing and emollients to fight dryness, but avoiding products with sensitizing potential is vital. Bath oils are most useful in conditions of the skin. A menthol-phenol preparation, for example Noxzema, is helpful as a counterirritant. The major sensitizing benefit of topical corticosteroids has to be weighed against all their potential side effects like corticosteroid addiction and depression of the steroid system in the body.
Oral antihistamines:
Oral medications have been used to treat pruritus, and antihistamines remain the cornerstone of oral therapy. The use of traditional histamine blockers has been limited by the sedative side effects, but all these medications in addition to working partly on pruritus have major side effects like drowsiness. In addition, many of the new drugs, which have been approved by the FDA, produce change in heart rate.
Morphine is the prototype of the class of opioid analgesic drugs which exert their effects by activating opioid receptors within the brain. When morphine is referred to individually in this application, this reference is meant to encompass other opioid drugs and is not meant to be morphine exclusively. Historically, narcotics have been used since the 18th century in the forms of oral or injectable morphine or opium in order to accomplish pain relief. Morphine is considered to be unsurpassed as an analgesic for severe pain.
Unfortunately, morphine and other opioid drugs have a number of severe side effects which hamper their widespread use and acceptance by both physicians and patients. These side effects include: addiction, nausea, inhibition of breathing, somnolence and dysphoria, all of which are mediated by morphine's action within the brain. It is still the current belief that narcotics ingested or injected will cross to the blood stream and from there go to the brain where there are morphine receptors. At that time, the narcotics are believed to attach to these morphine receptors and create a dullness of the pain but with all of the side effects described above. Of course, the worst potential effect is the addiction that can occur if the morphine is used beyond a few days or weeks on a continuous basis.
Reference is made to my earlier invention, made in conjunction with Dr. Christoph Stein, Ser. No. 08/291,614, filed Aug. 17, 1994 wherein the use of a topical application of opioid analgesic to alleviate pain is disclosed. This prior application discusses in detail the use of the topical application of the opioid analgesic and this discussion is incorporated in this application.